A Multicenter Study of Genotype Variation/Demographic Patterns in 2475 Individuals Including 1444 Cases With Breast Cancer in Turkey.

Objective: Breast cancer (BC) is the most common cancer type in women and may be inherited, mostly in an autosomal dominant pattern. The clinical diagnosis of BC relies on the published diagnostic criteria, and analysis of two genes, BRCA1 and BRCA2, which are strongly associated with BC, are included in these criteria. The aim of this study was to compare BC index cases with non-BC individuals in terms of genotype and diagnostic features to investigate the genotype/demographic information association. Materials and Methods: Mutational analyses for the BRCA1/BRCA2 genes was performed in 2475 individuals between 2013-2022 from collaborative centers across Turkey, of whom 1444 with BC were designated as index cases. Results: Overall, mutations were identified in 17% (421/2475), while the percentage of mutation carriers in cases of BC was similar, 16.6% (239/1444). BRCA1/BRCA2 gene mutations were detected in 17.8% (131/737) of familial cases and 12% (78/549) of sporadic cases. Mutations in BRCA1 were found in 4.9%, whereas 12% were in BRCA2 (p<0.05). Meta-analyses were performed to compare these results with other studies of Mediterranean-region populations. Conclusion: Patients with BRCA2 mutations were significantly more common than those with BRCA1 mutations. In sporadic cases, there was a lower proportion with BRCA1/BRCA2 variants, as expected, and these results were consistent with the data of Mediterranean-region populations. However, the present study, because of the large sample size, revealed more robust findings than previous studies. These findings may be helpful in facilitating the clinical management of BC for both familial and non-familial cases.

Improving locoregional outcome in high-intermediate-risk and high-risk stage I endometrial cancer with surgical staging followed by brachytherapy.

PURPOSE: This study aims to assess the locoregional efficacy of postoperative vaginal brachytherapy (VBT) alone in patients undergoing surgical staging for early-stage high-intermediate-risk (HIR) and high-risk (HR) endometrial cancer. MATERIALS AND METHODS: One hundred and four patients with early-stage HIR and HR endometrial cancer who underwent surgical staging were treated with adjuvant VBT alone. The patients with stage Ib, grade I-III, stage Ia, grade III, lower uterine segment involvement, and lymphovascular invasion (LVI) were included to study. RESULTS: The 5- and 10-year overall survival (OS) rates were 87% and 76%, respectively. The 5- and 10-year DFS rates were 86% and 86%, respectively. Among the patients, 92% had endometrioid adenocarcinoma, 2% had undifferentiated carcinoma, 2% had serous papillary carcinoma, and 4% had clear-cell carcinoma. Of the patients, 63% had stage Ib disease, while 37% had stage Ia disease. None of the patients had vaginal or pelvic lymph node recurrence, whereas two had para-aortic lymph node metastasis, one had surgical scar recurrence, one had para-aortic lymph node and brain metastasis, and one had lung metastasis. The presence of lymphatic invasion was found to be a statistically significant prognostic factor for increased distant metastasis rates (p = 0.020). Lymphatic invasion was also regarded as an independent prognostic factor for metastasis-free survival (p = 0.044). CONCLUSION: Our study results suggest that postoperative VBT alone is an effective and safe treatment modality with low complication in patients undergoing surgical staging for HIR and HR endometrial cancer.

Low pan-immune-inflammation-value predicts better chemotherapy response and survival in breast cancer patients treated with neoadjuvant chemotherapy.

Blood-based biomarkers reflect systemic inflammation status and have prognostic and predictive value in solid malignancies. As a recently defined biomarker, Pan-Immune-Inflammation-Value (PIV) integrates different peripheral blood cell subpopulations. This retrospective study of collected data aimed to assess whether PIV may predict the pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in Turkish women with breast cancer. The study consisted of 743 patients with breast cancer who were scheduled to undergo NAC before attempting cytoreductive surgery. A pre-treatment complete blood count was obtained in the two weeks preceding NAC, and blood-based biomarkers were calculated from absolute counts of relevant cell populations. The pCR was defined as the absence of tumor cells in both the mastectomy specimen and lymph nodes. Secondary outcome measures included disease-free survival (DFS) and overall survival (OS). One hundred seven patients (14.4%) had pCR. In receiver operating characteristic analysis, optimal cut-off values for the neutrophile-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte (PLR), PIV, and Ki-67 index were determined as ≥ 2.34, ≥ 0.22, ≥ 131.8, ≥ 306.4, and ≥ 27, respectively. The clinical tumor (T) stage, NLR, MLR, PLR, PIV, estrogen receptor (ER) status, human epidermal growth factor receptor-2 (HER-2) status, and Ki-67 index were significantly associated with NAC response in univariate analyses. However, multivariate analysis revealed that the clinical T stage, PIV, ER status, HER-2 status, and Ki-67 index were independent predictors for pCR. Moreover, the low PIV group patients had significantly better DFS and OS than those in the high PIV group (p = 0.034, p = 0.028, respectively). Based on our results, pre-treatment PIV seems as a predictor for pCR and survival, outperforming NLR, MLR, PLR in predicting pCR in Turkish women with breast cancer who received NAC. However, further studies are needed to confirm our findings.

The Ki-67 proliferation index predicts recurrence-free survival in patients with dermatofibrosarcoma protuberans.

Dermatofibrosarcoma protuberans (DFSP) is an uncommon soft tissue sarcoma that originates from the dermis or subcutaneous tissue in the skin. While its prognosis is generally favorable, disease recurrence is relatively frequent. Because morbidity after repeated surgery may be significant, an optimized prediction of recurrence-free survival (RFS) has the potential to improve current management strategies. The purpose of this study was to investigate the prognostic value of the Ki-67 proliferation index with respect to RFS in patients with DFSP. We retrospectively analyzed data from 45 patients with DFSP. We calculated the Ki-67 proliferation index as the percentage of immunostained nuclei among the total number of tumor cell nuclei regardless of the intensity of immunostaining. We constructed univariate and multivariate Cox proportional hazards regression models to identify predictors of RFS. Among the 45 patients included in the study, 8 developed local recurrences and 2 had lung metastases (median follow-up: 95.0 months; range: 5.2-412.4 months). The RFS rates at 60, 120, and 240 months of follow-up were 83.8%, 76.2%, and 65.3%, respectively. The median Ki-67 proliferation index was 14%. Notably, we identified the Ki-67 proliferation index as the only independent predictor for RFS in multivariate Cox proportional hazards regression analysis (hazard ratio = 1.106, 95% confidence interval = 1.019-1.200, p = 0.016). In summary, our results highlight the potential usefulness of the Ki-67 proliferation index for facilitating the identification of patients with DFSP at higher risk of developing disease recurrences.

Efficacy of Single-Dose Radiotherapy in Preventing Posttraumatic Tendon Adhesion.

Background and Aim Posttraumatic peritendinous adhesion is the greatest obstacle to achieve normal tendon function following lacerations of extrinsic flexor tendons of the hand. In this study, we aimed to evaluate whether single-dose radiotherapy (RT) has the potential to modulate intrasynovial tendon adhesions. Materials and Methods A total of 80 tendons from the third to fourth flexor profundus of both hind paws of 20 adult New Zealand rabbits were used in this study. Rabbits in the RT group received 3 Gy of X-irradiation in a single fraction. Histopathological evaluation of longitudinal sections of tendons was made using the Tang grading system for peritendinous adhesions. Intratendinous quality of the healing tissue in the laceration zone was assessed using a modified Movin scale. Results Adhesion and inflammatory response were greater in the RT group (p˂0.001). Tendon healing in the radiation group was found to be more uniform and organized compared with the control group. However, this difference was not statistically significant. The nuclei of the tenocytes in the radiation group showed a closer resemblance to normal tendon tissue when compared with the control group (p=0.007). Conclusions Despite RT's certain advantages such as extracorporeal use, anti-inflammatory effect, and homogenous tissue penetration, 3-Gy X-irradiation resulted in increased peritendinous posttraumatic adhesion, possibly due to dose imbalance. Increased roundness in the tenocyte nuclei was present in the RT group. Studies with different dosing regimens and a higher number of subjects are necessary to establish an ideal dose suppressing the synovial response without compromising tendon healing.

Clinicopathologic features and genetic characteristics of the BRCA1/2 mutation in Turkish breast cancer patients.

The aim of this study was to identify the frequency and spectrum of germline BRCA1/2 pathogenic alterations in a cohort of patients with breast carcinoma. In this study, a total of 603 breast cancer subjects from Turkey were screened for BRCA1/BRCA2 mutations using HDA and Sanger sequencing. In the present study, 21 BRCA1 and BRCA2 pathogenic variants were detected in 30 patients and BRCA1/2 mutations were significantly associated with a family history of breast/ovarian cancer. Analysis of overall survival for BRCA1/BRCA2 mutation carriers showed a trend for poor overall survival only in BRCA1 carriers, although this was not statistically significant in BRCA1 and BRCA2 mutation carriers. The c.5266dupC mutation is one of the most frequently reported mutations in BRCA1 and was identified in five breast cancer patients in our study. The most common BRCA2 gene mutations in the present study were c.8940delA and c.9097dupA, which were found in seven patients. We found mostly BRCA1 and BRCA2 mutation carriers in those patients who showed hormone-positive features. In conclusion, our data showed differences in the distribution of the mutation spectrum of BRCA1 and BRCA2 in Turkey.

Prediction of breast cancer metastasis risk using circulating tumor markers: A follow-up study.

Distant organ tumor dissemination is a major cause of breast cancer-related deaths. In 2010, we analyzed the prognostic importance of the circulating tumor markers (CTMs) cytokeratin 19 (CK19), CK20, epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) in relation to the clinical and pathological characteristics of patients with breast cancer (BC). To assess the clinical utility of CK19, CK20 and EGFR in predicting distant metastasis in BC, here we report 7-year follow-up results of 77 patients. The patients with at least one positive CTM were classified as CTM(+) and those negative for all CTMs were assigned to CTM(-) group. In patients who received no treatment following CTM analysis, 25.0% had metastasis in CTM(+) and 10.0% in CTM(-) group. In patients who received one of the following therapies: chemotherapy, radiotherapy or hormone therapy, or the combinations of these therapies, the rate of metastasis was 33.3% in CTM(+) and 20.0% in CTM(-) group. Disease-free time was shorter in CTM(+) patients compared to CTM(-) group (28.83 ± 10.76 and 41.38 ± 9.5 months, respectively). According to multivariate Cox proportional hazard regression analysis, the presence of regional lymph node metastasis, Ki-67 expression, higher tumor grade and CTM expression status were predictors of poor prognosis associated with distant metastasis (p < 0.05). Also, CTM positivity was a factor associated with metastasis-related poor prognosis (HR = 0.492, p = 0.026). The mean survival for CTM(+) patients was shorter than that for CTM(-) patients (90.671 ± 2.66 and 101.23 ± 3.92 months, respectively; p > 0.05). Our findings demonstrate that CTM positivity may indicate a high metastasis risk; however, CTM negativity does not guarantee low metastasis risk. These results may encourage further preclinical investigation of CTMs, to evaluate the possible implications of these findings to the clinical setting.

Enhancer of zeste homologue 2 (EZH2) expression in synovial sarcomas as a promising indicator of prognosis.

Synovial sarcoma (SS) is a type of soft-tissue sarcoma, often linked to poor survival. Although overexpression of enhancer of zeste homologue 2 (EZH2) has been associated with poor prognosis in different tumors, a few studies investigated this link in SS. Here, we analyzed the relationship between EZH2 expression and prognostic factors in SS. We included 29 patients with SS. Immunostaining of EZH2 was performed with (D2C9) XPTM Rabbit mAb antibody, and the results were classified as low EZH2 expression (negative or weak expression) and high EZH2 expression category (moderate or strong expression). Analysis of survival in relation to prognostic factors was performed with Kaplan-Meier survival curves and Cox proportional hazard regression analysis. Our sample included 19/29 female and 10/29 male patients, with age range 16-63 years. The tumor diameter ranged from 2 to 15 cm. Necrosis was observed in 15/29 cases. Sixteen cases had >10 mitoses per 50 high-power fields (HPFs). Out of 29 cases, 14 showed low and 15 had high EZH2 expression. Statistically significant results were obtained for the association between the presence of metastasis and necrosis (p = 0.042), high EZH2 expression and distant metastasis (p = 0.018), high EZH2 expression and necrosis (p = 0.016), and high EZH2 expression and the tumor size >5 cm versus tumor size ≤5 cm (p = 0.014). Patients with all of the following: the tumor size ≤5 cm, low EZH2 expression, and without necrosis and distant metastasis had significantly longer survival time. Our results are consistent with previous studies, suggesting that EZH2 overexpression is an indicator of poor prognosis in SS.

Radio-protective effect of cinnamic acid, a phenolic phytochemical, on genomic instability induced by X-rays in human blood lymphocytes in vitro.

The present study was designed to determine the protective activity of cinnamic acid against induction by X-rays of genomic instability in normal human blood lymphocytes. This radio-protective activity was assessed by use of the cytokinesis-block micronucleus test and the alkaline comet assay, with human blood lymphocytes isolated from two healthy donors. A Siemens Mevatron MD2 (Siemens AG, USA, 1994) linear accelerator was used for the irradiation with 1 or 2 Gy. Treatment of the lymphocytes with cinnamic acid prior to irradiation reduced the number of micronuclei when compared with that in control samples. Treatment with cinnamic acid without irradiation did not increase the number of micronuclei and did not show a cytostatic effect in the lymphocytes. The results of the alkaline comet assay revealed that cinnamic acid reduces the DNA damage induced by X-rays, showing a significant radio-protective effect. Cinnamic acid decreased the frequency of irradiation-induced micronuclei by 16-55% and reduced DNA breakage by 17-50%, as determined by the alkaline comet assay. Cinnamic acid may thus act as a radio-protective compound, and future studies may focus on elucidating the mechanism by which cinnamic acid offers radioprotection.

The evaluation of bcl-2 expression as a prognostic marker in early stage laryngeal cancer.

AIMS AND BACKGROUND: To evaluate the effect of bcl-2 expression on the local control and overall survival of patients with early stage laryngeal cancer treated with radiotherapy alone. METHODS AND STUDY DESIGN: We included 53 patients with stage Tis, T1, and T2 laryngeal cancer who were irradiated in our department. Paraffin blocks of all biopsy specimens were subjected to immunohistochemical analysis with a bcl-2 oncoprotein mouse clone 124 Scytek kit. RESULTS: The mean follow-up time was 61 months (range, 7-166). Local-regional recurrence was observed in 10 (19%) patients. Forty-three patients (81%) had negative bcl-2 staining, 5 patients (9%) had + staining, 3 patients (6%) ++ staining, and 2 patients (4%) +++ staining. No relationship was detected between bcl-2 expression and local control or overall survival. The emergence of a recurrence and a younger age (<50 years) were significantly related to poor overall survival (P = 0.000 and P = 0.021, respectively). Patients with hemoglobin levels in the middle of radiotherapy and at the end of radiotherapy higher than 13 g/dl had improved overall survival in multivariate analyses (P = 0.002 and P = 0.001, respectively). Regarding local control, the following were poor prognostic factors: smoking more than 20 cigarettes a day (P = 0.001) and being younger than 50 years of age (P = 0.001). CONCLUSIONS: No correlation was observed between bcl-2 expression and local control or overall survival. Whereas hemoglobin level, age and existence of a recurrence had a prognostic impact on overall survival, patient age and smoking status influenced local control rates.

Radioprotection by two phenolic compounds: chlorogenic and quinic acid, on X-ray induced DNA damage in human blood lymphocytes in vitro.

The present study was designed to determine the radioprotective effect of two phytochemicals, namely, quinic acid and chlorogenic acid, against X-ray irradiation-induced genomic instability in non-tumorigenic human blood lymphocytes. The protective ability of two phenolic acids against radiation-induced DNA damage was assessed using the alkaline comet assay in human blood lymphocytes isolated from two healthy human donors. A Siemens Mevatron MD2 (Siemens AG, USA, 1994) linear accelerator was used for irradiation. The results of the alkaline comet assay revealed that quinic acid and chlorogenic acid decreased the DNA damage induced by X-ray irradiation and provided a significant radioprotective effect. Quinic acid decreased the presence of irradiation-induced DNA damage by 5.99-53.57% and chlorogenic acid by 4.49-48.15%, as determined by the alkaline comet assay. The results show that quinic acid and chlorogenic acid may act as radioprotective compounds. Future studies should focus on determining the mechanism by which these phenolic acids provide radioprotection.

CK19, CK20, EGFR and HER2 status of circulating tumor cells in patients with breast cancer.

AIMS AND BACKGROUND: The major cause of death in breast cancer patients is metastasis. Various biomarkers have been used for the early detection of circulating tumor cells in the peripheral blood of breast cancer patients. The aims of the current study were to analyze circulating tumor cells in the blood of breast cancer patients by investigating EGFR, CK19, CK20 and HER2 expression profiles and to evaluate their prognostic importance. METHODS: CK19, CK20 and EGFR gene expression profiles were evaluated in the blood samples of 84 female patients with primary invasive ductal breast cancer and 20 healthy female volunteers using SYBR green-based real-time qPCR assays. HER2 expression analyses were conducted in 46 patients who had an HER2-positive primary tumor and in 30 healthy women to determine the cutoff level of positivity. RESULTS: The positive rates of CK20, EGFR, CK19 and HER2 mRNA expression in the peripheral blood were 28.57% (24/84), 20.23% (17/84), 5.95% (5/84) and 2.17% (1/46), respectively. The high positive ratio of CK20 mRNA expression in the peripheral blood of breast cancer was identified for the first time in the current study. Significant differences were identified in CK20 expression status and several clinical parameters related with aggressiveness of tumors using a binary logistic regression analysis. Higher CK20-positive levels were observed in patients who had lymph node metastasis and advanced-grade primary tumors, which were estrogen receptor-negative. We have demonstrated that CK20 may be a novel biomarker that is useful to identify circulating tumor cells and predict breast cancer progression. CONCLUSIONS: The results suggest that the investigation of CK20 mRNA with other biomarkers in the peripheral blood of breast cancer patients may be useful to monitor the presence of disseminated tumor cells in the blood circulation and to predict the prognosis of breast cancer.

Comparison of protracted infusion 5-fluorouracil and capecitabine in adjuvant chemoradiotherapy for rectal cancer.

BACKGROUND/AIMS: 5-Fluorouracil-based chemoradiotherapy is the most widely used treatment modality in the adjuvant treatment of rectal cancer. Capecitabine represents a valuable alternative to 5-Fluorouracil in this situation. METHODOLOGY: Patients with stage II and stage III rectal adenocarcinoma, who were included in this analysis, received adjuvant chemoradiotherapy consisting of external-beam radiotherapy (50.4-54Gy) either with 5-Fluorouracil at a median dose of 300 mg/m2/day by protracted venous infusion for 5 days a week, or capecitabine at a median dose of 1650 mg/m2/day for 5 days a week after surgery. The data concerning the toxicity and the efficacy of the treatments were compared in patients treated with 5-Fluorouracil- and capecitabine-based chemoradiotherapy. RESULTS: Forty-three patients received 5-Fluorouracil, and 24 patients received capecitabine during adjuvant radiotherapy. Although there were no differences between the groups in terms of toxicity rates, distant metastasis-free survival, disease-free survival, and overall survival rates; a trend for improved loco-regional recurrence-free survival rate was observed in the capecitabine arm (p = 0.063). CONCLUSIONS: Capecitabine is at least as effective as 5-Fluorouracil in the postoperative treatment of rectal adenocarcinoma. Considering the trend for improved loco-regional recurrence-free survival rate in the capecitabine arm, it seems that the drug exerts better synergy with radiotherapy in this situation.

Carcinoma originating from aberrant breast tissue. A case report and review of the literature.

Carcinoma arising from ectopic breast tissue, either supernumerary breast or aberrant breast tissue, is extremely rare. Carcinoma occurs more frequently in the ectopic breast tissue of the axilla than in extra-axillary ectopic breast tissue. Here we report a case of an invasive lobular carcinoma arising from extra-axillary ectopic breast tissue and presenting as a subcutaneous nodule.

Factors influencing axillary node metastasis in breast cancer.

AIMS AND BACKGROUND: The status of the axillary lymph nodes at the time of diagnosis has been accepted as one of the most important prognostic factors for the overall and disease-free survival of patients with breast cancer. The aim of our study was to determine which factors influence axillary node involvement in invasive breast cancer. METHODS: The data presented here were obtained from 344 patients who were treated for invasive breast cancer at the Department of Radiation Oncology, Uludag University Medical College, Bursa, Turkey. Possible prognostic factors were categorized as patient related and tumor related. The Mann-Whitney U test was used for univariate analysis and logistic regression was used for multivariate analysis. RESULTS: In univariate analysis, a familial cancer history (P = 0.0042), age < 40 years (P = 0.0276), higher T stage (P < 0.0000), nipple involvement (P = 0.0345), skin involvement (P = 0.0270), perineural invasion (P = 0.0231), and lymphatic vessel invasion (P < 0.0000) were correlated with increased axillary node involvement. A higher incidence of > or = 4 involved lymph nodes was associated with higher T stage (P = 0.0004), nipple involvement (P = 0.0292), presence of an extensive intraductal component (P = 0.0023), skin involvement (P = 0.0008), perineural invasion (P = 0.0523), and lymphatic vessel invasion (P < 0.0000) in univariate analysis. In multivariate analysis, age < 40 years (P = 0.0454), cancer history within the family (P = 0.0024), higher T stage (P = 0.0339), lymphatic vessel invasion (P = 0.0003), and perineural invasion (P = 0.0408) were found to be independent factors for axillary lymph node positivity. Age < 40 years (P = 0.0221), perineural invasion (P = 0.0408), and an extensive intraductal component (P = 0.0132) were associated with an increased incidence of > or = 4 involved nodes in the logistic regression analysis. In patients with breast cancer, the incidence of axillary lymph node involvement was independently influenced by age < 40 years, presence of cancer history within the family, higher T stage, lymphatic vessel invasion, and perineural invasion. CONCLUSIONS: In conclusion, absence of familial cancer history, presence of lymphatic vessel invasion, higher T stage, and age below 40 years independently increased the risk of axillary node involvement. Presence of perineural invasion and lymphatic vessel invasion, age below 40, and an extensive intraductal component of more than 25% independently affected the risk of having > or = 4 nodes involved. Patients characterized by these factors may be classified into a higher risk group for nodal involvement, but more data are needed to define factors that can help in the decision-making regarding the omission of axillary treatment.

Synchronous breast cancer in spouses.

Breast cancer in both spouses is extremely rare. There are 7 metachronous cases and 1 synchronous case in the English literature. No case has been reported in which 1 of the spouses had bilateral breast cancer. In this paper, we report a synchronous pair of cases where 1 of the spouses (wife) had bilateral breast cancer and the other (husband) had breast cancer.

Phase II study of induction chemotherapy with gemcitabine plus 5-fluorouracil followed by gemcitabine-based concurrent chemoradiotherapy for unresectable locally advanced pancreatic cancer.

AIMS AND BACKGROUND: To evaluate the efficacy and tolerability of a new treatment approach including induction chemotherapy (CT) and concurrent chemoradiotherapy (CRT) in unresectable, locally advanced pancreatic cancer (LAPC). PATIENTS AND METHODS: Twenty-four patients with LAPC were enrolled in the study. They first received induction CT consisting of 5-fluorouracil (5FU) (500 mg/m2) and gemcitabine (1000 mg/m2), which were given weekly for 3 weeks of every 4. Patients showing a response or disease stabilization after 2 cycles of induction CT received CRT consisting of external beam radiotherapy (50.4-54 Gy in fractions of 1.8 Gy/day) and gemcitabine (350 mg/m2, weekly for 6 weeks). Patients without disease progression received 2 additional cycles of CT consisting of 5FU plus gemcitabine with the same doses and schedule as given in the induction CT. RESULTS: After the end of the study, 2 (8%) and 5 (21%) patients showed complete and partial responses, respectively. Five patients (21%) had disease stabilization. The grade 3 and 4 toxicities associated with CT were neutropenia (21%) and thrombocytopenia (4%). The grade 3 and 4 toxicities occurring in patients who received CRT were neutropenia (24%), thrombocytopenia (24%), diarrhea (18%), and nausea (12%). The median progression-free survival for all patients was 6 months (95% CI, 3.6-8.4), and the median overall survival was 11 months (95% CI, 8.16-13.84). CONCLUSIONS: The CRT approach of this study is moderately active and has an acceptable toxicity profile. However, the incorporation of combination CT into CRT at the present schedule could not produce any additional benefit over CRT alone. Newer agents with more systemic activity are clearly warranted.

Evaluation of infections in non-small cell lung cancer patients treated with radiotherapy.

PURPOSE: We aim to determine infections occurring in patients with non-small cell lung cancer during radiotherapy (RT). METHODS AND MATERIALS: A total of 181 patients had been treated with thoracic radiotherapy between October 1995 and December 1999. Radiotherapy was given using 1.8-3Gray (Gy) fraction daily, five fractions a week for a total dose of 59.4Gy (30-70.2Gy). A complete history was collected retrospectively for each patient. All microbiological examinations were performed according to the routine procedures of the hospital laboratory. Numeric and categoric variables were employed such as sex, age, performance status, histology, stage, chemotherapy, usage of corticosteroids, neutropenia, surgery, hospitalization, associated diseases, smoking during treatment, package per year of cigarette smoking, dose of radiotherapy, and response rates. RESULTS: Infections developed in 84 patients (46%, 84/181) during thoracic radiotherapy. A 101 episodes of infections developed in these patients. Most patients suffered from sputum production (65%), cough (59%), auscultation findings (31%) and fever (31%). Gram-negative bacteria were the most frequently isolated pathogens in the cultures of specimens (70%, 16/23 samples). Neoadjuvant chemotherapy (OR=4.81; 95% CI, 1.57-9.12; p=0.003) and neutropenia (OR=4.25; 95% CI, 1.44-6.89; p=0.009) were found as risk factors for influencing infection based on logistic regression analyses. Package per year of cigarette smoking was found statistically significantly higher in patients with infections than patients without infections (p=0.001). A slight increase in infections, which was of borderline statistical significance (p=0.07), was observed in patients age over 70. Ciprofloxacin and clarithromycin were the most frequently used agents in treatment. Median survival was 9 months in the patients with infection and 13 months in the 97 patients without infection. Overall survival seemed to be statistically significantly better in patients without infection than patients with infection (p=0.042) calculated using Kaplan-Meier method. Based on Cox regression analyses; overall survival was not correlated to presence of infection but associated with poor performance status (5940 cGy (OR=2.06; 95% CI, 0.72-7.18; p=0.007) and the absence of response to treatment (OR=2.45; 95% CI, 0.89-14.23; p<0.001) were also found to be risk factors for survival. CONCLUSIONS: Infections are important causes of morbidity and mortality in lung cancer patients. The control of infection in these patients may improve the survival. Predisposing factors and treatment management approaches in non-small cell lung cancer should be defined carefully.